首页|基于网络药理学和实验验证探讨宣白承气汤治疗急性肺损伤的作用机制

基于网络药理学和实验验证探讨宣白承气汤治疗急性肺损伤的作用机制

扫码查看
基于网络药理学和动物实验探讨宣白承气汤治疗急性肺损伤(acute lung injury,ALI)的作用机制。通过网络药理学获得宣白承气汤调控ALI的潜在靶点及信号通路。通过动物实验构建ALI大鼠模型,给予不同剂量组的宣白承气汤治疗后,用苏木精-伊红(hematoxylin-eosin staining,HE)染色检测大鼠肺组织病理变化;酶联免疫吸附测定(enzyme-linked immunosorbent assay,ELISA)法测定大鼠外周血白细胞介素-6(interleukin-6,IL-6)、白细胞介素-1β(interleukin-1β,IL-1β)及肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)水平;实时荧光定量PCR(quantitative real-time PCR,qPCR)验证磷脂酰肌醇 3-激酶/蛋白激酶 B/哺乳动物雷帕霉素靶蛋白(phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin,PI3K/Akt/mTOR)信号通路中mRNA表达水平;蛋白免疫印迹(Western blot)法测定大鼠PI3K/Akt/mTOR信号通路相关蛋白表达情况。网络药理学显示,共得到宣白承气汤治疗ALI的化合物 52 个,作用靶点 112 个,ALI疾病靶点 4 723 个,"药物-疾病"交集靶点 94 个,主要活性成分为β-谷甾醇、大黄素、豆甾醇、光甘草定和芦荟大黄素等;关键靶点为TNF、IL-1β、前列腺素内过氧化物合酶 2(prostaglandin-endoperoxide synthase 2,PTGS2)和肿瘤蛋白 53(tumor protein 53,TP53)等;主要涉及脂质与动脉粥样硬化、p53 信号通路、IL-17 信号通路、PI3K/Akt 信号通路等。动物实验显示,与模型组相比,宣白承气汤能减轻ALI大鼠肺组织病理损伤程度,降低ALI大鼠血清中IL-6、IL-1β、TNF-α水平,下调PI3K、Akt、mTOR mRNA表达,下调PI3K、Akt、mTOR、p-PI3K/PI3K、p-Akt/Akt及p-mTOR/mTOR蛋白的表达。结果表明,宣白承气汤能通过多成分、多靶点及多途径发挥治疗ALI的作用。同时,宣白承气汤可能通过抑制PI3K/Akt/mTOR信号通路,减轻炎症反应,改善ALI大鼠肺损伤状态。
Mechanism of Xuanbai Chengqi Decoction in treating acute lung injury based on network pharmacology and experimental verification
This study aims to investigate the mechanism of Xuanbai Chengqi Decoction in treating acute lung injury(ALI)based on network pharmacology and animal experiments.The potential targets and signaling pathways of Xuanbai Chengqi Decoction in regulating ALI were predicted by network pharmacology.The rat model of ALI was constructed and administrated with different doses of Xuanbai Chengqi Decoction.The pathological changes in the lung tissue of rats were observed by hematoxylin-eosin(HE)staining.The levels of interleukin-6(IL-6),interleukin-1β(IL-1β),and tumor necrosis factor-α(TNF-α)in the peripheral blood were measured by enzyme-linked immunosorbent assay(ELISA).The mRNA and protein levels of factors in the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)/mammalian target of rapamycin(mTOR)signaling pathway were determined by quantitative real-time PCR(qPCR)and Western blot,respectively.A total of 52 compounds from Xuanbai Chengqi Decoction were predicted to be involved in the treatment of ALI,including β-sitosterol,emodin,stigmasterol,glabridin,and aloe-emodin,which corresponded to 112 targets,and 4 723 targets of ALI were predicted.The compounds and ALI shared 94 common targets.The key targets included TNF,IL-1β,prostaglandin-endoperoxide synthase 2(PTGS2),and tumor protein 53(TP53).Lipids and atherosclerosis,p53 signaling pathway,IL-17 signaling pathway,and PI3K/Akt signaling pathway were mainly involved in the treatment.Animal experiments showed that compared with the model group,Xuanbai Chengqi Decoction alleviated the pathological changes in the lung tissue,lowered the serum levels of IL-6,IL-1β,and TNF-α,down-regulated the mRNA and protein levels of PI3K,Akt,and mTOR,and reduced the p-PI3K/PI3K,p-Akt/Akt,and p-mTOR/mTOR ratios in ALI rats.The results showed that Xuanbai Chengqi Decoction exerted its therapeutic effects on ALI via multiple components,targets,and pathways.Meanwhile,Xuanbai Chengqi Decoction may reduce the inflammation and attenuate the lung injuries of ALI rats by inhibiting the PI3K/Akt/mTOR signaling pathway.

Xuanbai Chengqi Decoctionacute lung injurynetwork pharmacologyphosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin signaling pathwaymechanism

罗成、叶远航、姜成、宁博、柯佳、陈刚

展开 >

湖北中医药大学 中医学院,湖北 武汉 430061

湖北省中医院/湖北中医药大学附属医院/湖北省中医药研究院,湖北 武汉 430074

陕西中医药大学 第一临床医学院,陕西 咸阳 712000

湖北中医药大学 基础医学院,湖北 武汉 430061

展开 >

宣白承气汤 急性肺损伤 网络药理学 磷脂酰肌醇3-激酶/蛋白激酶B/哺乳动物雷帕霉素靶蛋白信号通路 机制

国家中医药管理局传承工作室建设项目湖北省自然科学基金(联合基金)项目湖北省公共卫生青年拔尖人才培养计划

国中医药办人教函[2022]245号2023AFD173鄂卫通[2021]74号

2024

中国中药杂志
中国药学会

中国中药杂志

CSTPCD北大核心
影响因子:1.718
ISSN:1001-5302
年,卷(期):2024.49(16)